Next Article in Journal
Association of Cerebral Venous Thrombosis with mRNA COVID-19 Vaccines: A Disproportionality Analysis of the World Health Organization Pharmacovigilance Database
Next Article in Special Issue
Humoral Immune Response of BNT162b2 and CoronaVac Vaccinations in Hemodialysis Patients: A Multicenter Prospective Cohort
Previous Article in Journal
Immunogenicity and Safety of Homologous and Heterologous Prime–Boost Immunization with COVID-19 Vaccine: Systematic Review and Meta-Analysis
Previous Article in Special Issue
Impact of Moderna mRNA-1273 Booster Vaccine on Fully Vaccinated High-Risk Chronic Dialysis Patients after Loss of Humoral Response
 
 
Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
Journals
Vaccines
Volume 10
Issue 5
10.3390/vaccines10050800
vaccines-logo
Submit to this Journal Review for this Journal Propose a Special Issue
► Article Menu

Article Menu

share Share announcement Help format_quote Cite question_answer Discuss in SciProfiles thumb_up
...
Endorse textsms
...
Comment
first_page
settings
Order Article Reprints
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Review

Vaccination for the Prevention of Infection among Immunocompromised Patients: A Concise Review of Recent Systematic Reviews

by
Kay Choong See
Division of Respiratory & Critical Care Medicine, Department of Medicine, National University Hospital, Singapore 119228, Singapore
Vaccines 2022, 10(5), 800; https://doi.org/10.3390/vaccines10050800
Submission received: 17 April 2022 / Revised: 10 May 2022 / Accepted: 16 May 2022 / Published: 18 May 2022
(This article belongs to the Special Issue Vaccines for Patients With Immunodeficiencies and Their Efficacy: An Overview in Pandemic Era)
Review Reports Versions Notes

Abstract

:
Vaccination is crucial for avoiding infection-associated morbidity and mortality among immunocompromised patients. However, immunocompromised patients respond less well to vaccinations compared to healthy people, and little is known about the relative efficacy of various vaccines among different immunocompromised states. A total of 54 systematic reviews (22 COVID-19; 32 non-COVID-19) published within the last 5 years in Pubmed® were reviewed. They demonstrated similar patterns within three seroconversion response categories: good (about >60% when compared to healthy controls), intermediate (~40–60%), and poor (about <40%). Good vaccine responses would be expected for patients with chronic kidney disease, human immunodeficiency virus infection (normal CD4 counts), immune-mediated inflammatory diseases, post-splenectomy states, and solid tumors. Intermediate vaccine responses would be expected for patients with anti-cytotoxic T-lymphocyte antigen-4 therapy, hematologic cancer, and human immunodeficiency virus infection (low CD4 counts). Poor vaccine responses would be expected for patients with B-cell-depleting agents (e.g., anti-CD20 therapy), hematopoietic stem-cell transplant, solid organ transplant, and liver cirrhosis. For all vaccine response categories, vaccination should be timed when patients are least immunosuppressed. For the intermediate and poor vaccine response categories, high-dose vaccine, revaccination when patients are less immunosuppressed, checking for seroconversion, additional booster doses, and long-acting monoclonal antibodies may be considered, supplemented by shielding measures.

1. Introduction

Immunocompromised patients have weakened immune systems due to chronic illness (e.g., chronic kidney failure) or therapies that depress immunity (e.g., chemotherapy for cancer, immunomodulation for immune-mediated diseases, and anti-rejection drugs for organ transplantation). Consequently, immunocompromised patients suffer increased susceptibility to sepsis. Sepsis, which is the combination of severe infection with a dysregulated response to infection and organ dysfunction [1], is in turn associated with increased morbidity, mortality, and cost of care.
To improve the overall prognosis for immunocompromised patients, both downstream improvements of sepsis care and upstream prevention of infection are crucial. For the latter, vaccination against common pathogens is a key strategy which is recommended by major guidelines [2]. Common vaccine-preventable pathogens include those transmitted via the respiratory route (e.g., SARS-CoV-2, influenza, pneumococcus, and varicella-zoster virus) and those transmitted via other routes (e.g., viral hepatitis A and B, and yellow fever virus). Given the risk of proliferation of attenuated vaccine strains in immunocompromised patients [3], live virus vaccines are contraindicated in patients with active immunosuppression and are only allowed after careful balancing of benefit versus risk [4]. Concerns about vaccine-related relapse of inflammatory rheumatic diseases and post-vaccination allograft rejection exist; however, in general, these appear uncommon [5,6,7,8], and vaccinations should not be withheld on the basis of these concerns [2].
However, just as immunocompromised patients have deficient immunity to defend against infection, such patients may also have deficient immune responses to vaccination, rendering the latter less effective than expected from studies among healthy controls. Substantial reductions in vaccine efficacy (measured within controlled study environments) or effectiveness (measured in real-world studies) using standard vaccination regimes would necessitate enhanced vaccination strategies or the addition of non-vaccine-based preventive methods (e.g., shielding measures).
Systematic reviews on vaccination for the prevention of infection in immunocompromised patients are ideal for aggregating the published literature on individual vaccines and individual immunocompromising conditions. Given that immunocompromised patients are a heterogeneous group with varying levels of immunosuppression, subgroups of immunocompromising conditions with varying vaccine responses may be identified. Knowledge of these patient subgroups may help stratify preventive measures, with more intensive measures being provided for patients with the poorest vaccine response. A review of systematic reviews was, therefore, conducted to elucidate broad immunocompromised patient subgroups. In doing so, this paper can serve as a source of information for readers interested in an overview of studies, as well as stimulate further research into host-dependent classification of vaccine effectiveness.

2. Materials and Methods

Using a validated systematic review filter [9], a comprehensive search of Pubmed® (pubmed.ncbi.nlm.nih.gov) was performed (Table 1). To study contemporary and clinically relevant vaccines, the search was limited to papers published within 5 years of 13 April 2022. Studies were excluded if vaccination against infection was not studied, study outcome was not about vaccine efficacy/effectiveness, patients were not immunocompromised, or primary studies were not reviewed.
Screening of titles and abstracts was conducted, and the following data fields were extracted from the full-text documents: vaccine type, number of adult and pediatric patients, number of studies, the reason for being immunocompromised, description of vaccine efficacy, and interventions to improve vaccine efficacy. A qualitative review of included studies was then performed to uncover a general understanding of the associations of various immunocompromising conditions with immune responses to vaccines, as well as construct vaccine seroconversion response categories. In addition, interventions to improve vaccine efficacy were reviewed to inform potential solutions for various vaccine seroconversion response categories.

3. Results

Out of 979 studies extracted from Pubmed®, 54 systematic reviews (22 COVID-19; 32 non-COVID-19) were included (Table 1).

3.1. Systematic Reviews of COVID-19 Vaccines

A total of 22 systematic reviews focused on COVID-19 vaccines (Table 2). Most the COVID-19 vaccines were mRNA-based, while the remainder were viral vector-based and inactivated virus vaccines. Immunocompromised states studied included use of B-cell-depleting anti-CD20 therapy, chronic kidney failure, immune-mediated inflammatory diseases, malignancy, and solid organ transplant recipients.
The COVID-19 vaccine systematic reviews predominantly used seroconversion as a marker for vaccine efficacy. In general, the studies showed that patients with chronic kidney failure on dialysis (not requiring organ transplantation) [10,11,12], immune-mediated inflammatory diseases [13,14,15,16], and solid tumors [17] had seroconversion rates that were high and similar to healthy controls (seroconversion rates among patients ranged from about 83% to 97%). In contrast, patients with receipt of anti-CD20 therapy [18] and solid organ transplants [11,19,20] (thus requiring anti-rejection immunosuppression) had markedly low vaccine seroconversion rates (rates ranged from about 26% to 45% after two vaccine doses). Patients with hematologic cancers had intermediate seroconversion rates (rates ranged from about 54% to 65%) [21,22,23,24,25,26,27,28]. An intervention that improved vaccine efficacy was the use of additional booster vaccine doses [20].
Table
Table 2. Efficacy of COVID-19 vaccination among immunocompromised patients.
Table 2. Efficacy of COVID-19 vaccination among immunocompromised patients.
Vaccine TypeAuthor (Year) [Ref]Number of IC Patients (Studies)Reason for being ICDescription of Vaccine EfficacyInterventions to Improve Vaccine Efficacy
COVID-19 (mRNA)Akyol
(2021) [10]		1955 adults (18)Dialysis and kidney transplant recipientsPooled seroconversion rate of 27.2% for kidney transplantation, 88.5% for dialysis patients, and 100% for healthy controls after two doses of vaccineSecond vaccine dose
COVID-19 (various)Becerril-Gaitan
(2022) [21]		8332 adults (35)MalignancyPooled seroconversion rate in cancer patients of 51% after first dose vaccine and 73% after second dose vaccine. Seroconversion lower in patients with hematologic cancer versus solid tumors (65% vs. 94%)Second vaccine dose
COVID-19
(various)		Bhurwal (2022) [13]2484 adults (21)Inflammatory bowel diseasePooled seroconversion rate of 73.7% and 96.8% after one and two doses of vaccine respectivelySecond vaccine dose
COVID-19 (mostly mRNA)Cavanna (2021) [22]621 adults (6)MalignancyNo reduced rate of seroconversion for patients with solid tumors compared with the control, but 38% reduced seroconversion for patients with hematologic cancerSecond vaccine dose
COVID-19 (various)Corti (2022) [23]9260 adults (36)MalignancyPooled seroconversion rate of 11–87.5% and 7.3–100% after one and two doses of vaccine, respectively. Exceptionally poor seroconversion for patients with hematologic cancer receiving B-cell-depleting agents within last 12 monthsSecond vaccine dose
COVID-19 (mRNA)Efros
(2022) [19]		853 adults (7)Solid organ transplant recipientsPooled seroconversion rate of 50.3% after the third vaccineThird vaccine dose
COVID-19 (various)Gagelmann
(2021) [24]		11,086 adults (49)Hematologic malignanciesPooled seroconversion rate of 64% after 2 doses of mRNA or 1 dose of vector-based vaccines, versus 96% for solid cancer and 98% for healthy controlsNot studied
COVID-19 (various)Galmiche
(2022) [25]		25,209 adults (162)Malignancy, dialysis, transplant recipients, immune-mediated diseaseNo seroconversion among 18–100% of solid organ transplant recipients, 14–61% of patients with hematological malignancy, 2–36% of patients with cancer, and 2–30% of patients on dialysisNot studied
COVID-19 (mRNA, viral vector)Guven
(2021) [27]		1448 adults (17)MalignancyCancer patients had significantly lower seroconversion rates than controls after first vaccine dose (37.3 vs. 74.1%) and after two doses (78.3 vs. 99.6%). The difference in seroconversion rates was more pronounced patients with hematologic cancer versus solid tumors Second vaccine dose
COVID-19
(mRNA, viral vector)		Guven
(2022) [26]		3187 adults (26)Hematologic malignanciesPooled seroconversion rate of 33.3% and 65.3% after one and two doses of vaccine, respectively; <70% seroconversion if on anti-CD20 or anti-CTLA-4 therapySecond vaccine dose
COVID-19 (mRNA)Jena (2022) [15]2286 adults (25)Immune mediated inflammatory diseasesPooled seroconversion rate 69.3% and 83.1%, after 1 and 2 doses of mRNA vaccination, respectivelySecond dose vaccine
COVID-19 (various)Jena (2022) [14]9447 adults (46)Inflammatory bowel diseasePooled seroconversion rate of 96% for complete vaccination. Decay of titers higher with anti-TNF immunomodulationNot studied
COVID-19 (94% mRNA)Lee
(2022) [29]		9974 adults (82)Malignancy, immune-mediated inflammatory disorders, organ transplant recipients, HIV patients Seroconversion 6–44% after 1 vaccine dose, 35–89% after 2 vaccine dosesSecond vaccine dose
COVID-19
(99% mRNA)		Ma (2022) [11]4264 adults (27)Chronic kidney failure requiring kidney replacement therapyAfter 2 vaccine doses, 44% decreased seropositivity compared to general population. Kidney transplant recipients had significantly lower seroconversion than patients on hemodialysis or peritoneal dialysis (26.1 vs. 84.3% and 92.4%, respectively)Not studied
COVID-19 (mRNA)Manothum-metha (2022) [20]11,713 adults (29)Solid organ transplant recipientsMean seroconversion rate was 10.4% after 1 dose, 44.9% after 2 doses, and 63.1% after 3 doses. Lower response given older age, deceased donor status, and use of immunosuppression (antimetabolite, rituximab, and antithymocyte globulin)Multiple (up to 4) vaccine doses
COVID-19
(various)		Marra
(2022) [30]		45,040 adults (24)Solid organ transplant recipients, malignancy, inflammatory rheumatic diseasesMean seroconversion rate of 25.2% in solid organ transplant recipients, 68% in patients with malignancy, and 86% in patients with inflammatory rheumatic diseases. Overall vaccine effectiveness of 70.4% against symptomatic infection Not studied
COVID-19
(various)		Mehrabi
(2022) [31]		3207 adults (26)Autoimmune conditions, malignancy, transplant recipientsA 48% lower rate of seroconversion after 2 doses, worse with transplant recipientsNot studied
COVID-19
(mostly mRNA)		Sakuraba
(2022) [17]		1453 adults (16)MalignancyPooled seroconversion rate of 54.2% and 87.7% after one and two doses of vaccine, respectively; lower rates with hematologic compared to solid organ malignancySecond vaccine dose
COVID-19
(mostly mRNA)		Sakuraba (2022) [16]5360 adults (25)Immune-mediated inflammatory diseasesPooled seroconversion rate of 73.2% and 83.4% after one and two doses of vaccine, respectively; lower rates with patients on anti-CD20 therapySecond vaccine dose
COVID-19
(various)		Schietzel
(2022) [18]		1342 adults (23)Anti-CD20 therapyPooled seroconversion rate of 40% for complete vaccination; lower rates with kidney transplant recipientsNot studied
COVID-19
(various)		Swai (2022) [12]2789 adults (27)Chronic kidney failureHemodialysis patients’ proportions of humoral (antibody) and cellular (T-helper cell) immune responses varied from 87.3% to 88.8% and from 62.9% to 85.8%, respectively, comparable to healthy control responses. Kidney transplant patients’ humoral and cellular immune responses ranged from 2.6% to 29.9% and from 5.1% to 59.8%, respectively, significantly lower than healthy control responsesNot studied
COVID-19
(various)		Teh
(2022) [28]		7064 adults (44)Hematologic malignanciesOverall seroconversion rate 37–51% after 1 dose of COVID-19 vaccine and 62–66% after 2 dosesSecond vaccine dose
CTLA-4: cytotoxic T-lymphocyte antigen-4; HIV: human immunodeficiency virus; IC: immunocompromised; mRNA: messenger ribonucleic acid; Ref: reference; TNF: tumor necrosis factor. Various vaccine types included mRNA, viral vector-based, and inactivated virus vaccines.

3.2. Systematic Reviews of Non-COVID-19 Vaccines

A total of 32 systematic reviews focused on non-COVID-19 vaccines (Table 3). Several vaccines were studied, including inactivated hepatitis A vaccine [32], recombinant hepatitis B vaccine [33,34,35,36,37,38], recombinant human papillomavirus vaccines [39,40], inactivated influenza vaccine [41,42,43,44,45,46,47,48,49,50,51], live-attenuated measles vaccine (given post hematopoietic stem-cell transplantation [52] and in children living with human immunodeficiency virus [53]), pneumococcal conjugate and polysaccharide vaccines [46,49,54,55,56], live-attenuated and recombinant subunit zoster vaccines [57,58], live-attenuated yellow fever vaccine [59], and others [60,61,62,63]. Immunocompromised states studied included use of B-cell-depleting anti-CD20 therapy, chronic kidney failure, human immunodeficiency virus infection, immune-mediated inflammatory diseases, liver cirrhosis, malignancy, post-splenectomy status, and solid organ transplant recipients.
The non-COVID-19 vaccine systematic reviews predominantly used seroconversion as a marker for vaccine efficacy. In general, the studies showed that patients with immune-mediated inflammatory diseases [33,34,38,43,46,47,49,61], human immunodeficiency virus infection [35,37,39,40], post-splenectomy status [55], and solid tumors [48] had seroconversion rates that were high and similar to healthy controls (seroconversion rates among patients ranged from about 61% to 100%). In contrast, patients with receipt of anti-CD20 therapy [50], solid organ transplants [32,42], and liver cirrhosis [36] had markedly low vaccine seroconversion rates (rates ranged from about 3% to 49%). Patients with hematologic cancers [58] had intermediate seroconversion rates (about 52%). Systematic reviews involving children [35,39,40,42,44,52,53,54,59,60,61,62,63] demonstrated findings consistent with those involving adults. An intervention that improved vaccine efficacy was the use of high-dose vaccines [35,37,42,44,45,51].

4. Discussion

4.1. Overview of Results

According to the humoral responses to vaccines of various immunocompromising conditions, the systematic reviews for COVID-19 and non-COVID-19 vaccines demonstrated similar patterns. Given the absence of any validated guidelines or recommendations for classification of vaccine seroconversion, three seroconversion response categories were arbitrarily constructed from the data: good (about >60% when compared to healthy controls), intermediate (~40–60%), and poor (about <40%) (Table 4). Good vaccine responses would be expected for patients with chronic kidney disease, human immunodeficiency virus infection with normal CD4 counts, immune-mediated inflammatory diseases, post-splenectomy states, and solid tumors. Intermediate vaccine responses would be expected for patients with anti-cytotoxic T-lymphocyte antigen-4 therapy, hematologic cancer, and human immunodeficiency virus infection with low CD4 counts. Poor vaccine responses would be expected for patients with B-cell-depleting agents (e.g., anti-CD20 therapy), hematopoietic stem-cell transplant, solid organ transplant, and liver cirrhosis.
For all vaccine response categories, vaccination should be timed when patients are least immunosuppressed (e.g., before initiating immunosuppressive treatment) and when immunosuppressive disease states are optimally treated [64]. For the intermediate and poor vaccine response categories, methods to improve vaccine response include the use of high-dose vaccine and revaccination when patients are less immunosuppressed. These vaccine-based methods should also be supplemented by non-vaccine methods such as shielding measures (e.g., face mask use, hand hygiene, and physical distancing for respiratory pathogens). For the poor vaccine response category, given possible vaccine nonresponse, seroconversion may be checked. If nonresponse is demonstrated, additional booster doses may be considered [11,20,65]. Alternatively, long-acting monoclonal antibodies for pre-exposure prophylaxis may be considered in patients at high risk of acquiring serious infection [66].

4.2. Limitations of the Current Study

Firstly, this review only analyzed systematic reviews included in Pubmed®, which would not encompass systematic reviews included in other databases such as Embase©. Nonetheless, the individual systematic reviews would have included papers from both Pubmed®-listed and non-Pubmed®-listed journals, and missing important data are, hence, unlikely. Secondly, this review was limited to the last 5 years of publication, which would exclude older systematic reviews covering other vaccines. However, this would avoid the inclusion of noncontemporary vaccines, which might affect the overall pattern of vaccine efficacy among immunocompromised patients. Thirdly, this review did not include a quality assessment of individual systematic reviews, as it was the intention to be as inclusive as possible. Nevertheless, the studies all showed fairly consistent results, and stratification by study quality would not have affected the overall interpretation of the current findings. Fourthly, given the heterogeneity of studies, statistical pooling of the results could not be performed, although the current results may serve as a source of information for readers interested in an overview of studies. Lastly, systematic reviews were not available for studying the interaction of immune-mediated diseases and many immunosuppressive medications or for studying combinations of immunocompromised states. Logically, the vaccine response is expected to worsen with greater doses or number of immunosuppressive medications and with coexisting immunocompromised states.

4.3. Limitations of the Included Systematic Reviews

Although a substantial number of non-COVID-19 vaccine systematic reviews contained data from children [35,39,40,42,44,52,53,54,59,60,61,62,63] (13 out of 32), none of the COVID-19 vaccine systematic reviews included pediatric studies. Furthermore, none of the systematic reviews had long-term vaccine efficacy or effectiveness results, and none were performed for oral vaccines (e.g., oral rotavirus, oral cholera, oral polio, and oral typhoid). These important knowledge gaps could potentially be filled once more primary studies are available.

4.4. Future Directions

Vaccine development is often a long process involving multiple rounds of preclinical studies and clinical trials. Even for clinically successful vaccines, eventual vaccine efficacy would be dependent on both pathogen and host [67,68]. From this study, according to the systematic reviews focusing on vaccines targeting a variety of pathogens, the type of immunosuppression in the host appears to play an important role. This review provides a broad overview of various vaccine studies, leading to the construction of three seroconversion response categories. Further studies, which include prediction of vaccination efficacy using baseline measures of circulating B cells [69], could be performed to refine these categories and to highlight exceptions within these categories. These categories should also be validated against long-term serological protection and clinical effectiveness data. In addition, interventions to improve vaccine efficacy are limited and more studies are required to investigate novel methods such as heterologous prime-boost techniques [70] and long-acting preventive antibody therapy [66].

5. Conclusions

In conclusion, this review of 54 systematic reviews demonstrated three vaccine seroconversion response categories among immunocompromised patients: good (about >60% when compared to healthy controls), intermediate (~40–60%), and poor (about <40%). For all vaccine response categories, vaccination should be timed when patients are least immunosuppressed. For the intermediate and poor vaccine response categories, high-dose vaccine, revaccination when patients are less immunosuppressed, checking for seroconversion, additional booster doses, and long-acting monoclonal antibodies may be considered, supplemented by shielding measures.

Funding

This research received no external funding.

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

Data supporting this review are available in the reference section.

Conflicts of Interest

The author declares no conflict of interest.

References

  1. Singer, M.; Deutschman, C.S.; Seymour, C.W.; Shankar-Hari, M.; Annane, D.; Bauer, M.; Bellomo, R.; Bernard, G.R.; Chiche, J.D.; Coopersmith, C.M.; et al. The third international consensus definitions for sepsis and septic shock (sepsis-3). JAMA 2016, 315, 801–810. [Google Scholar] [CrossRef]
  2. Rubin, L.G.; Levin, M.J.; Ljungman, P.; Davies, E.G.; Avery, R.; Tomblyn, M.; Bousvaros, A.; Dhanireddy, S.; Sung, L.; Keyserling, H.; et al. 2013 idsa clinical practice guideline for vaccination of the immunocompromised host. Clin. Infect. Dis. 2014, 58, 309–318. [Google Scholar] [CrossRef]
  3. Schrauder, A.; Henke-Gendo, C.; Seidemann, K.; Sasse, M.; Cario, G.; Moericke, A.; Schrappe, M.; Heim, A.; Wessel, A. Varicella vaccination in a child with acute lymphoblastic leukaemia. Lancet 2007, 369, 1232. [Google Scholar] [CrossRef]
  4. Huber, F.; Ehrensperger, B.; Hatz, C.; Chappuis, F.; Buhler, S.; Eperon, G. Safety of live vaccines on immunosuppressive or immunomodulatory therapy-a retrospective study in three swiss travel clinics. J. Travel Med. 2018, 25, tax082. [Google Scholar] [CrossRef]
  5. Del Bello, A.; Marion, O.; Delas, A.; Congy-Jolivet, N.; Colombat, M.; Kamar, N. Acute rejection after anti-SARS-CoV-2 mRNA vaccination in a patient who underwent a kidney transplant. Kidney Int. 2021, 100, 238–239. [Google Scholar] [CrossRef]
  6. Dos Santos, G.; Haguinet, F.; Cohet, C.; Webb, D.; Logie, J.; Ferreira, G.L.; Rosillon, D.; Shinde, V. Risk of solid organ transplant rejection following vaccination with seasonal trivalent inactivated influenza vaccines in england: A self-controlled case-series. Vaccine 2016, 34, 3598–3606. [Google Scholar] [CrossRef] [Green Version]
  7. Stevens, E.; Weinblatt, M.E.; Massarotti, E.; Griffin, F.; Emani, S.; Desai, S. Safety of the zoster vaccine recombinant adjuvanted in rheumatoid arthritis and other systemic rheumatic disease patients: A single center’s experience with 400 patients. ACR Open Rheumatol. 2020, 2, 357–361. [Google Scholar] [CrossRef]
  8. Nakafero, G.; Grainge, M.J.; Myles, P.R.; Mallen, C.D.; Zhang, W.; Doherty, M.; Nguyen-Van-Tam, J.S.; Abhishek, A. Association between inactivated influenza vaccine and primary care consultations for autoimmune rheumatic disease flares: A self-controlled case series study using data from the clinical practice research datalink. Ann. Rheum. Dis. 2019, 78, 1122–1126. [Google Scholar] [CrossRef] [Green Version]
  9. Avau, B.; Van Remoortel, H.; De Buck, E. Translation and validation of pubmed and embase search filters for identification of systematic reviews, intervention studies, and observational studies in the field of first aid. J. Med. Libr. Assoc. 2021, 109, 599–608. [Google Scholar] [CrossRef]
  10. Akyol, M.; Cevik, E.; Ucku, D.; Tanriover, C.; Afsar, B.; Kanbay, A.; Covic, A.; Ortiz, A.; Basile, C.; Kanbay, M. Immunogenicity of SARS-CoV-2 mrna vaccine in dialysis and kidney transplant patients: A systematic review. Tuberk. Toraks 2021, 69, 547–560. [Google Scholar] [CrossRef]
  11. Ma, B.M.; Tam, A.R.; Chan, K.W.; Ma, M.K.M.; Hung, I.F.N.; Yap, D.Y.H.; Chan, T.M. Immunogenicity and safety of COVID-19 vaccines in patients receiving renal replacement therapy: A systematic review and meta-analysis. Front. Med. 2022, 9, 827859. [Google Scholar] [CrossRef]
  12. Swai, J.; Gui, M.; Long, M.; Wei, Z.; Hu, Z.; Liu, S. Humoral and cellular immune response to severe acute respiratory syndrome coronavirus-2 vaccination in haemodialysis and kidney transplant patients. Nephrology 2022, 27, 7–24. [Google Scholar] [CrossRef]
  13. Bhurwal, A.; Mutneja, H.; Bansal, V.; Goel, A.; Arora, S.; Attar, B.; Minacapelli, C.D.; Kochhar, G.; Chen, L.A.; Brant, S.; et al. Effectiveness and safety of SARS-CoV-2 vaccine in inflammatory bowel disease patients: A systematic review, meta-analysis and meta-regression. Aliment. Pharmacol. Ther. 2022, 55, 1244–1264. [Google Scholar] [CrossRef]
  14. Jena, A.; James, D.; Singh, A.K.; Dutta, U.; Sebastian, S.; Sharma, V. Effectiveness and durability of COVID-19 vaccination in 9447 patients with ibd: A systematic review and meta-analysis. Clin. Gastroenterol. Hepatol. 2022. [Google Scholar] [CrossRef]
  15. Jena, A.; Mishra, S.; Deepak, P.; Kumar, M.P.; Sharma, A.; Patel, Y.I.; Kennedy, N.A.; Kim, A.H.J.; Sharma, V.; Sebastian, S. Response to SARS-CoV-2 vaccination in immune mediated inflammatory diseases: Systematic review and meta-analysis. Autoimmun. Rev. 2022, 21, 102927. [Google Scholar] [CrossRef]
  16. Sakuraba, A.; Luna, A.; Micic, D. Serologic response to coronavirus disease 2019 (COVID-19) vaccination in patients with immune-mediated inflammatory diseases: A systematic review and meta-analysis. Gastroenterology 2022, 162, 88–108.e109. [Google Scholar] [CrossRef]
  17. Sakuraba, A.; Luna, A.; Micic, D. Serologic response following SARS-CoV2 vaccination in patients with cancer: A systematic review and meta-analysis. J. Hematol. Oncol. 2022, 15, 15. [Google Scholar] [CrossRef]
  18. Schietzel, S.; Anderegg, M.; Limacher, A.; Born, A.; Horn, M.P.; Maurer, B.; Hirzel, C.; Sidler, D.; Moor, M.B. Humoral and cellular immune responses on SARS-CoV-2 vaccines in patients with anti-cd20 therapies: A systematic review and meta-analysis of 1342 patients. RMD Open 2022, 8, e002036. [Google Scholar] [CrossRef]
  19. Efros, O.; Anteby, R.; Halfon, M.; Meisel, E.; Klang, E.; Soffer, S. Efficacy and safety of third dose of the COVID-19 vaccine among solid organ transplant recipients: A systemic review and meta-analysis. Vaccines 2022, 10, 95. [Google Scholar] [CrossRef]
  20. Manothummetha, K.; Chuleerarux, N.; Sanguankeo, A.; Kates, O.S.; Hirankarn, N.; Thongkam, A.; Dioverti-Prono, M.V.; Torvorapanit, P.; Langsiri, N.; Worasilchai, N.; et al. Immunogenicity and risk factors associated with poor humoral immune response of SARS-CoV-2 vaccines in recipients of solid organ transplant: A systematic review and meta-analysis. JAMA Netw. Open 2022, 5, e226822. [Google Scholar] [CrossRef]
  21. Becerril-Gaitan, A.; Vaca-Cartagena, B.F.; Ferrigno, A.S.; Mesa-Chavez, F.; Barrientos-Gutierrez, T.; Tagliamento, M.; Lambertini, M.; Villarreal-Garza, C. Immunogenicity and risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection after coronavirus disease 2019 (COVID-19) vaccination in patients with cancer: A systematic review and meta-analysis. Eur. J. Cancer 2022, 160, 243–260. [Google Scholar] [CrossRef]
  22. Cavanna, L.; Citterio, C.; Toscani, I. COVID-19 vaccines in cancer patients. Seropositivity and safety. Systematic review and meta-analysis. Vaccines 2021, 9, 1048. [Google Scholar] [CrossRef]
  23. Corti, C.; Antonarelli, G.; Scotte, F.; Spano, J.P.; Barriere, J.; Michot, J.M.; Andre, F.; Curigliano, G. Seroconversion rate after vaccination against COVID-19 in patients with cancer-a systematic review. Ann. Oncol. 2022, 33, 158–168. [Google Scholar] [CrossRef]
  24. Gagelmann, N.; Passamonti, F.; Wolschke, C.; Massoud, R.; Niederwieser, C.; Adjalle, R.; Mora, B.; Ayuk, F.; Kroger, N. Antibody response after vaccination against SARS-CoV-2 in adults with haematological malignancies: A systematic review and meta-analysis. Haematologica 2021. [Google Scholar] [CrossRef]
  25. Galmiche, S.; Luong Nguyen, L.B.; Tartour, E.; de Lamballerie, X.; Wittkop, L.; Loubet, P.; Launay, O. Immunological and clinical efficacy of COVID-19 vaccines in immunocompromised populations: A systematic review. Clin. Microbiol. Infect. 2022, 28, 163–177. [Google Scholar] [CrossRef]
  26. Guven, D.C.; Sahin, T.K.; Akin, S.; Uckun, F.M. Impact of therapy in patients with hematologic malignancies on seroconversion rates after SARS-CoV-2 vaccination. Oncologist 2022, 27, e357–e361. [Google Scholar] [CrossRef]
  27. Guven, D.C.; Sahin, T.K.; Kilickap, S.; Uckun, F.M. Antibody responses to COVID-19 vaccination in cancer: A systematic review. Front. Oncol. 2021, 11, 759108. [Google Scholar] [CrossRef]
  28. Teh, J.S.K.; Coussement, J.; Neoh, Z.C.F.; Spelman, T.; Lazarakis, S.; Slavin, M.A.; Teh, B.W. Immunogenicity of COVID-19 vaccines in patients with hematologic malignancies: A systematic review and meta-analysis. Blood Adv. 2022, 6, 2014–2034. [Google Scholar] [CrossRef]
  29. Lee, A.; Wong, S.Y.; Chai, L.Y.A.; Lee, S.C.; Lee, M.X.; Muthiah, M.D.; Tay, S.H.; Teo, C.B.; Tan, B.K.J.; Chan, Y.H.; et al. Efficacy of COVID-19 vaccines in immunocompromised patients: Systematic review and meta-analysis. BMJ 2022, 376, e068632. [Google Scholar] [CrossRef]
  30. Marra, A.R.; Kobayashi, T.; Suzuki, H.; Alsuhaibani, M.; Tofaneto, B.M.; Bariani, L.M.; Auler, M.A.; Salinas, J.L.; Edmond, M.B.; Doll, M.; et al. Short-term effectiveness of COVID-19 vaccines in immunocompromised patients: A systematic literature review and meta-analysis. J. Infect. 2022, 84, 297–310. [Google Scholar] [CrossRef]
  31. Mehrabi Nejad, M.M.; Moosaie, F.; Dehghanbanadaki, H.; Haji Ghadery, A.; Shabani, M.; Tabary, M.; Aryannejad, A.; SeyedAlinaghi, S.; Rezaei, N. Immunogenicity of COVID-19 mrna vaccines in immunocompromised patients: A systematic review and meta-analysis. Eur. J. Med. Res. 2022, 27, 23. [Google Scholar] [CrossRef]
  32. Garcia Garrido, H.M.; Veurink, A.M.; Leeflang, M.; Spijker, R.; Goorhuis, A.; Grobusch, M.P. Hepatitis a vaccine immunogenicity in patients using immunosuppressive drugs: A systematic review and meta-analysis. Travel Med. Infect. Dis. 2019, 32, 101479. [Google Scholar] [CrossRef]
  33. Jiang, H.Y.; Wang, S.Y.; Deng, M.; Li, Y.C.; Ling, Z.X.; Shao, L.; Ruan, B. Immune response to hepatitis b vaccination among people with inflammatory bowel diseases: A systematic review and meta-analysis. Vaccine 2017, 35, 2633–2641. [Google Scholar] [CrossRef]
  34. Kochhar, G.S.; Mohan, B.P.; Khan, S.R.; Chandan, S.; Kassab, L.L.; Ponnada, S.; Desai, A.; Caldera, F.; Dulai, P.S.; Farraye, F.A. Hepatitis-b vaccine response in inflammatory bowel disease patients: A systematic review and meta-analysis. Inflamm. Bowel Dis. 2021, 27, 1610–1619. [Google Scholar] [CrossRef]
  35. Lee, J.H.; Hong, S.; Im, J.H.; Lee, J.S.; Baek, J.H.; Kwon, H.Y. Systematic review and meta-analysis of immune response of double dose of hepatitis b vaccination in hiv-infected patients. Vaccine 2020, 38, 3995–4000. [Google Scholar] [CrossRef]
  36. Rodrigues, I.C.; Silva, R.; Felicio, H.C.C.; Silva, R.F.D. New immunization schedule effectiveness against hepatitis b in liver transplantation patients. Arq. Gastroenterol. 2019, 56, 440–446. [Google Scholar] [CrossRef]
  37. Tian, Y.; Hua, W.; Wu, Y.; Zhang, T.; Wang, W.; Wu, H.; Guo, C.; Huang, X. Immune response to hepatitis b virus vaccine among people living with hiv: A meta-analysis. Front Immunol. 2021, 12, 745541. [Google Scholar] [CrossRef]
  38. Singh, A.K.; Jena, A.; Mahajan, G.; Mohindra, R.; Suri, V.; Sharma, V. Meta-analysis: Hepatitis b vaccination in inflammatory bowel disease. Aliment. Pharmacol. Ther. 2022, 55, 908–920. [Google Scholar] [CrossRef]
  39. Mavundza, E.J.; Wiyeh, A.B.; Mahasha, P.W.; Halle-Ekane, G.; Wiysonge, C.S. A systematic review of immunogenicity, clinical efficacy and safety of human papillomavirus vaccines in people living with the human immunodeficiency virus. Hum. Vaccin. Immunother. 2020, 16, 426–435. [Google Scholar] [CrossRef]
  40. Zizza, A.; Banchelli, F.; Guido, M.; Marotta, C.; Di Gennaro, F.; Mazzucco, W.; Pistotti, V.; D’Amico, R. Efficacy and safety of human papillomavirus vaccination in hiv-infected patients: A systematic review and meta-analysis. Sci Rep. 2021, 11, 4954. [Google Scholar] [CrossRef]
  41. Bitterman, R.; Eliakim-Raz, N.; Vinograd, I.; Zalmanovici Trestioreanu, A.; Leibovici, L.; Paul, M. Influenza vaccines in immunosuppressed adults with cancer. Cochrane Database Syst. Rev. 2018, 2, CD008983. [Google Scholar] [CrossRef]
  42. Chong, P.P.; Handler, L.; Weber, D.J. A systematic review of safety and immunogenicity of influenza vaccination strategies in solid organ transplant recipients. Clin. Infect. Dis. 2018, 66, 1802–1811. [Google Scholar] [CrossRef] [Green Version]
  43. Huang, Y.; Wang, H.; Tam, W.W.S. Is rheumatoid arthritis associated with reduced immunogenicity of the influenza vaccination? A systematic review and meta-analysis. Curr. Med. Res. Opin. 2017, 33, 1901–1908. [Google Scholar] [CrossRef]
  44. Lai, J.J.; Lin, C.; Ho, C.L.; Chen, P.H.; Lee, C.H. Alternative-dose versus standard-dose trivalent influenza vaccines for immunocompromised patients: A meta-analysis of randomised control trials. J. Clin. Med. 2019, 8, 590. [Google Scholar] [CrossRef] [Green Version]
  45. Leibovici Weissman, Y.; Cooper, L.; Sternbach, N.; Ashkenazi-Hoffnung, L.; Yahav, D. Clinical efficacy and safety of high dose trivalent influenza vaccine in adults and immunosuppressed populations—A systematic review and meta-analysis. J. Infect. 2021, 83, 444–451. [Google Scholar] [CrossRef]
  46. Muller, K.E.; Dohos, D.; Sipos, Z.; Kiss, S.; Dembrovszky, F.; Kovacs, N.; Solymar, M.; Eross, B.; Hegyi, P.; Sarlos, P. Immune response to influenza and pneumococcal vaccines in adults with inflammatory bowel disease: A systematic review and meta-analysis of 1429 patients. Vaccine 2022, 40, 2076–2086. [Google Scholar] [CrossRef]
  47. Nguyen, J.; Hardigan, P.; Kesselman, M.M.; Demory Beckler, M. Immunogenicity of the influenza vaccine in multiple sclerosis patients: A systematic review and meta-analysis. Mult. Scler. Relat. Disord. 2021, 48, 102698. [Google Scholar] [CrossRef]
  48. Spagnolo, F.; Boutros, A.; Croce, E.; Cecchi, F.; Arecco, L.; Tanda, E.; Pronzato, P.; Lambertini, M. Influenza vaccination in cancer patients receiving immune checkpoint inhibitors: A systematic review. Eur. J. Clin. Investig. 2021, 51, e13604. [Google Scholar] [CrossRef]
  49. Subesinghe, S.; Bechman, K.; Rutherford, A.I.; Goldblatt, D.; Galloway, J.B. A systematic review and metaanalysis of antirheumatic drugs and vaccine immunogenicity in rheumatoid arthritis. J. Rheumatol. 2018, 45, 733–744. [Google Scholar] [CrossRef]
  50. Vijenthira, A.; Gong, I.; Betschel, S.D.; Cheung, M.; Hicks, L.K. Vaccine response following anti-cd20 therapy: A systematic review and meta-analysis of 905 patients. Blood Adv. 2021, 5, 2624–2643. [Google Scholar] [CrossRef]
  51. Zhang, W.; Sun, H.; Atiquzzaman, M.; Sou, J.; Anis, A.H.; Cooper, C. Influenza vaccination for hiv-positive people: Systematic review and network meta-analysis. Vaccine 2018, 36, 4077–4086. [Google Scholar] [CrossRef]
  52. Groeneweg, L.; Loeffen, Y.G.T.; Versluys, A.B.; Wolfs, T.F.W. Safety and efficacy of early vaccination with live attenuated measles vaccine for hematopoietic stem cell transplant recipients and solid organ transplant recipients. Vaccine 2021, 39, 3338–3345. [Google Scholar] [CrossRef]
  53. Mehtani, N.J.; Rosman, L.; Moss, W.J. Immunogenicity and safety of the measles vaccine in hiv-infected children: An updated systematic review. Am. J. Epidemiol. 2019, 188, 2240–2251. [Google Scholar] [CrossRef]
  54. Adawi, M.; Bragazzi, N.L.; McGonagle, D.; Watad, S.; Mahroum, N.; Damiani, G.; Conic, R.; Bridgewood, C.; Mahagna, H.; Giacomelli, L.; et al. Immunogenicity, safety and tolerability of anti-pneumococcal vaccination in systemic lupus erythematosus patients: An evidence-informed and prisma compliant systematic review and meta-analysis. Autoimmun. Rev. 2019, 18, 73–92. [Google Scholar] [CrossRef]
  55. Lenzing, E.; Rezahosseini, O.; Burgdorf, S.K.; Nielsen, S.D.; Harboe, Z.B. Efficacy, immunogenicity, and evidence for best-timing of pneumococcal vaccination in splenectomized adults: A systematic review. Expert Rev. Vaccines 2022, 21, 723–733. [Google Scholar] [CrossRef]
  56. van Aalst, M.; Langedijk, A.C.; Spijker, R.; de Bree, G.J.; Grobusch, M.P.; Goorhuis, A. The effect of immunosuppressive agents on immunogenicity of pneumococcal vaccination: A systematic review and meta-analysis. Vaccine 2018, 36, 5832–5845. [Google Scholar] [CrossRef]
  57. Hamad, M.A.; Allam, H.; Sulaiman, A.; Murali, K.; Cheikh Hassan, H.I. Systematic review and meta-analysis of herpes zoster vaccine in patients with ckd. Kidney Int. Rep. 2021, 6, 1254–1264. [Google Scholar] [CrossRef]
  58. Racine, E.; Gilca, V.; Amini, R.; Tunis, M.; Ismail, S.; Sauvageau, C. A systematic literature review of the recombinant subunit herpes zoster vaccine use in immunocompromised 18–49 year old patients. Vaccine 2020, 38, 6205–6214. [Google Scholar] [CrossRef]
  59. Martin, C.; Domingo, C.; Bottieau, E.; Buonfrate, D.; De Wit, S.; Van Laethem, Y.; Dauby, N. Immunogenicity and duration of protection after yellow fever vaccine in people living with human immunodeficiency virus: A systematic review. Clin. Microbiol. Infect. 2021, 27, 958–967. [Google Scholar] [CrossRef]
  60. Adetokunboh, O.O.; Ndwandwe, D.; Awotiwon, A.; Uthman, O.A.; Wiysonge, C.S. Vaccination among hiv-infected, hiv-exposed uninfected and hiv-uninfected children: A systematic review and meta-analysis of evidence related to vaccine efficacy and effectiveness. Hum. Vaccin Immunother. 2019, 15, 2578–2589. [Google Scholar] [CrossRef] [Green Version]
  61. Dembinski, L.; Dziekiewicz, M.; Banaszkiewicz, A. Immune response to vaccination in children and young people with inflammatory bowel disease: A systematic review and meta-analysis. J. Pediatr. Gastroenterol. Nutr. 2020, 71, 423–432. [Google Scholar] [CrossRef]
  62. Keller, M.; Pittet, L.F.; Zimmermann, P. Immunogenicity and safety of routine vaccines in children and adolescents with rheumatic diseases on immunosuppressive treatment—A systematic review. Eur. J. Pediatr. 2022, 181, 1329–1362. [Google Scholar] [CrossRef]
  63. Tse, H.N.; Borrow, R.; Arkwright, P.D. Immune response and safety of viral vaccines in children with autoimmune diseases on immune modulatory drug therapy. Expert Rev. Vaccines 2020, 19, 1115–1127. [Google Scholar] [CrossRef]
  64. Soy, M.; Keser, G.; Atagunduz, P.; Mutlu, M.Y.; Gunduz, A.; Koybasi, G.; Bes, C. A practical approach for vaccinations including COVID-19 in autoimmune/autoinflammatory rheumatic diseases: A non-systematic review. Clin. Rheumatol. 2021, 40, 3533–3545. [Google Scholar] [CrossRef]
  65. Ludwig, H.; Boccadoro, M.; Moreau, P.; San-Miguel, J.; Cavo, M.; Pawlyn, C.; Zweegman, S.; Facon, T.; Driessen, C.; Hajek, R.; et al. Recommendations for vaccination in multiple myeloma: A consensus of the european myeloma network. Leukemia 2021, 35, 31–44. [Google Scholar] [CrossRef]
  66. Bruel, T.; Hadjadj, J.; Maes, P.; Planas, D.; Seve, A.; Staropoli, I.; Guivel-Benhassine, F.; Porrot, F.; Bolland, W.H.; Nguyen, Y.; et al. Serum neutralization of SARS-CoV-2 omicron sublineages ba.1 and ba.2 in patients receiving monoclonal antibodies. Nat. Med. 2022. [Google Scholar] [CrossRef]
  67. Langwig, K.E.; Gomes, M.G.M.; Clark, M.D.; Kwitny, M.; Yamada, S.; Wargo, A.R.; Lipsitch, M. Limited available evidence supports theoretical predictions of reduced vaccine efficacy at higher exposure dose. Sci. Rep. 2019, 9, 3203. [Google Scholar] [CrossRef]
  68. Dhakal, S.; Klein, S.L. Host factors impact vaccine efficacy: Implications for seasonal and universal influenza vaccine programs. J. Virol. 2019, 93, e00797-19. [Google Scholar] [CrossRef]
  69. Diks, A.M.; Overduin, L.A.; van Leenen, L.D.; Slobbe, L.; Jolink, H.; Visser, L.G.; van Dongen, J.J.M.; Berkowska, M.A. B-cell immunophenotyping to predict vaccination outcome in the immunocompromised—A systematic review. Front. Immunol. 2021, 12, 690328. [Google Scholar] [CrossRef]
  70. Palgen, J.L.; Feraoun, Y.; Dzangue-Tchoupou, G.; Joly, C.; Martinon, F.; Le Grand, R.; Beignon, A.S. Optimize prime/boost vaccine strategies: Trained immunity as a new player in the game. Front. Immunol. 2021, 12, 612747. [Google Scholar] [CrossRef]
Table
Table 1. Study selection and reasons for exclusion.
Table 1. Study selection and reasons for exclusion.
Study Inclusion/Exclusion CriteriaNumber of Studies
Pubmed search performed on 13 April 2022, for articles published within the last 5 years. Search terms: (“vaccine” [MeSH] OR “vaccination” [MeSH] OR vaccine [All Fields] OR vaccination [All Fields] OR vaccine* [All Fields]) AND (“cancer” [MeSH] OR “cancer” OR “malignancy” OR “malign*” OR “immunocompromise” [All Fields] OR “immunocompromised” [All Fields] OR “immunodeficiency” [All Fields] OR “immunodeficient” [All Fields] OR “immunodef*” [All Fields] OR “immunocompr*” [All Fields] OR “chemotherapy” [All Fields] OR “chemo*” [All Fields] OR “immunosuppressed” [All Fields] OR “immunosuppression” [All Fields] OR “immunosupp*” [All Fields] OR “rheumatology” [All Fields] OR “rheumatic” [All Fields] OR “rheum*” [All Fields] OR “autoimmune” [All Fields] OR “autoimmunity” [All Fields] OR “transplant” [All Fields] OR “solid organ” [All Fields] OR steroids [MeSH] OR antineoplastic agents [MeSH] OR chemotherapy [MeSH] OR cytotoxicity [MeSH] OR immunologic [MeSH] OR antirheumatic agents [MeSH] OR immunosuppressive agents [MeSH] or steroid* or corticosteroid* or (antineoplastic* AND agent*) OR chemotherap* or cytotoxic*) AND ((“Meta-Analysis as Topic” [MeSH] OR meta analy* [TIAB] OR metaanaly* [TIAB] OR “Meta-Analysis” [PT] OR “Systematic Review” [PT] OR “Systematic Reviews as Topic” [MeSH] OR systematic review* [TIAB] OR systematic overview* [TIAB] OR “Review Literature as Topic” [MeSH]) OR (cochrane [TIAB] OR embase [TIAB] OR psychlit [TIAB] OR psyclit [TIAB] OR psychinfo [TIAB] OR psycinfo [TIAB] OR cinahl [TIAB] OR cinhal [TIAB] OR “science citation index” [TIAB] OR bids [TIAB] OR cancerlit [TIAB]) OR (reference list* [TIAB] OR bibliograph* [TIAB] OR hand-search* [TIAB] OR “relevant journals” [TIAB] OR manual search* [TIAB]) OR ((“selection criteria” [TIAB] OR “data extraction” [TIAB]) AND “Review” [PT])) NOT (“Comment” [PT] OR “Letter” [PT] OR “Editorial” [PT] OR (“Animals” [MeSH] NOT (“Animals” [MeSH] AND “Humans” [MeSH])))979
Exclusion 1: Vaccination against infection not studied590
Exclusion 2: Study outcome was not about vaccine efficacy/effectiveness170
Exclusion 3: Patients were not immunocompromised120
Exclusion 4: Primary studies were not systematically reviewed45
Included in final review54
Table
Table 3. Efficacy of non-COVID-19 vaccination among immunocompromised patients.
Table 3. Efficacy of non-COVID-19 vaccination among immunocompromised patients.
Vaccine TypeAuthor (Year) [Ref]Number of IC Patients (Studies)Reason for Being ICDescription of Vaccine EfficacyInterventions to Improve Vaccine Efficacy
HAVGarcia (2019) [32]1332 adults (17)Organ transplant recipients, or chronic inflammatory conditionsIn organ transplant recipients, seroconversion was 0–67% after 1 dose and 0–97% after 2 doses. In patients with chronic inflammatory conditions, seroconversion was 6–100% after 1 dose and 48–100% after 2 dosesSecond vaccine dose
HBVJiang (2017) [33]1688 adults (13)Inflammatory bowel diseasePooled seroconversion response rate 61%, better for younger patients, when vaccinated during disease remission or when not on immunosuppressionVaccination ideally done before starting immune-suppression or during disease remission
HBVKochhar (2021) [34]2375 adults (14)Inflammatory bowel diseasePooled proportion of adequate immune response 64%, with 87% reduced odds of response vs. healthy controlsNot studied
HBVLee (2020) [35]914 adults, 56 children (9)HIV99% increased odds of vaccine seroconversion response among patients who received a double (40 mcg) vs. standard (20 mcg) doseDouble better than single dose
HBVRodrigues (2019) [36]Not stated (24)Liver disease requiring transplantSeroconversion 20–54% for cirrhotic patients vs. 74–97% for healthy controls. No seroconversion superiority between the accelerated (3 months) vs. conventional (6 months) immunization schedulesAccelerated immunization schedules
HBVTian (2021) [37]1821 adults (17)HIVPooled seroconversion rate of 71.5%, worse with lower CD4 countsDouble better than single dose. Four-dose schedule better than three-dose schedule
HBVSingh
(2022) [38]		2602 adults (21)Inflammatory bowel disease62% adequate immune response (>10 IU/L) and 42% effective immune response (>100 IU/L), worsened with immunosuppressionNot studied
HPVMavundza (2020) [39]916 adults, 126 children (5)HIV96–100% seroconversion rate for both bivalent and quadrivalent vaccinesNot studied
HPVZizza (2021) [40]950 adults/children (4)HIV~100% seroconversion rate for all 3 vaccines studiedNot studied
InfluenzaBitterman (2018) [41]2275 adults (6)CancerGenerally decreased mortality, influenza-like illness and pneumoniaAdjuvanted vaccine (inconclusive)
InfluenzaChong (2018) [42]943 adults/children (7)Organ transplant recipientsSeroconversion (7–63.9%) rates for influenza antigens were low and not improved by intradermal or adjuvanted
influenza vaccines. Some benefit from high dose (60 mcg) vaccine and booster doses, compared to standard single dose (15 mcg)		Alternative vaccine strategies (intradermal; adjuvanted; high-dose; booster doses)
InfluenzaHuang (2017) [43]886 adults (13)Rheumatoid arthritisSimilar seroconversion compared to healthy controls, and 44–49% lower for patients receiving non-steroid immunosuppressionAdjuvanted vaccine more immunogenic than non-adjuvanted
Influenza (trivalent)Lai (2019) [44]888 adults, 132 children (8)Transplant or chemo-therapy recipientsHigh-dose vaccine (60 mcg) increased seroconversion over standard dose (15 mcg) by 13% for A/H1N1 strains, and was well-toleratedHigh vs. standard dose
Influenza (trivalent)Leibovici (2021) [45]41,313 adults (3)Older adults ≥65 years and IC24% decreased risk of laboratory-confirmed influenza for high-dose (60 mcg) vs. low-dose (15 mcg) vaccineHigh dose (4×) trivalent vaccine
InfluenzaMuller
(2022) [46]		644 adults (7)Inflammatory bowel diseaseNo differences in antibody responses were observed compared to non-immunosuppressed patientsNot studied
InfluenzaNguyen (2021) [47]332 adults (9)Multiple sclerosis on treatmentNo difference in antibody response in multiple sclerosis patients vs. healthy controlsNot studied
InfluenzaSpagnolo (2021) [48]986 adults (8)Immune checkpoint inhibitor therapy for cancerSeroconversion rate 52–65% from one study. No differences in terms of antibody titers compared with healthy age-matched controls from another studyNot studied
InfluenzaSubesinghe (2018) [49]350 adults (7)Rheumatoid arthritisInfluenza vaccine humoral responses preserved with methotrexate and tumor necrosis factor inhibitor exposure. Combined methotrexate and tocilizumab/tofacitinib associated with reduced pneumococcal and influenza vaccine humoral responsesNot studied
InfluenzaVijenthira (2021) [50]222 adults (13)Anti-CD20 therapyPooled seroconversion 3% after 1 pandemic influenza vaccine dose, 95% less than healthy controlsNot studied
InfluenzaZhang (2018) [51]2015 adults (13)HIVAdjuvanted 7.5 mcg booster and 60 mcg single vaccine strategies provided 2–3 times better seroconversion and seroprotection outcomes, than single 15 mcg vaccineHigh dose (4×) vaccine; adjuvanted vaccine
Measles (live attenuated)Groeneweg (2021) [52]319 children (10)Transplant recipientsSeroconversion rates 41–100% after 1 dose and 73–100% after 2 doses in solid organ transplant recipients; 33–100% after 1 dose and 100% after 2 doses in hematopoietic stem-cell transplant recipientsNot studied
MeaslesMehtani (2019) [53]335 children (12)HIV30–56% decreased seroconversion in HIV-infected children vs. uninfected controlsNot studied
PneumococcalAdawi (2019) [54]571 adults, 30 children (18)SLEProtective antibody titers 36–97.6%, lower with high erythrocyte sedimentation rate, older age, earlier SLE onset, high disease activity, and immunosuppressive therapyNot studied
PneumococcalLenzing
(2022) [55]		2430 adults (21)Post-splenectomyNo differences in antibody responses were observed compared to healthy controlsOptimal vaccination timing but results were uncertain
PneumococcalMuller
(2022) [46]		785 adults (5)Inflammatory bowel diseaseNo decreased seropositivity with non-anti-TNF therapy and 72% decreased seropositivity with anti-TNF therapy, compared to non-immunosuppressed patientsNot studied
PneumococcalSubesinghe (2018) [49]141 adults (2)Rheumatoid arthritisMethotrexate associated with reduced pneumococcal vaccine humoral response. Combined methotrexate and tocilizumab/tofacitinib associated with reduced pneumococcal and influenza vaccine humoral responsesNot studied
Pneumococcalvan Aalst (2018) [56]1623 adults (22)Autoimmune disease receiving immuno-suppressionAfter PCV vaccination, 26% seroconversion among patients vs. 47% among controls. After PPSV, seroconversion 37% among patients vs. 50% among controlsNot studied
VZV (ZVL or VZVsub)Hamad (2021) [57]404,561 adults (8)Chronic kidney failure including transplant patients45% lower risk of VZV in vaccinated patients vs. controls, but no effect for the subgroup of transplant patientsNot studied
VZV (VZVsub)Racine (2020) [58]1389 adults (6)Various patient groups eHumoral immune response 50–93%; 52% for patients with hematological malignancy. Vaccine efficacy against infection was 67–72% in hematopoietic stem-cell transplant patientsNot studied
Yellow fever (live attenuated)Martin (2021) [59]561 adults, 18 children (10)HIV97.6% seroconversionNot studied
Various aAdeto-kunboh (2019) [60]66,220 children (14)HIVPneumococcal vaccine efficacy (to prevent disease) 32% for HIV-infected vs. 78% for HIV-uninfected. BCG protection 0% for HIV-infected vs. 59% for HIV-uninfected. Hib protection 44% for HIV-infected vs. 97% for HIV-uninfected. Rotavirus vaccines similar protection for HIV-infected and HIV-uninfectedNot studied
Various bDembinski (2020) [61]1130 patients, 10–24 years (20)Inflammatory bowel diseaseImmunogenicity of vaccinations not altered by IBD status or use of immunosuppressionNot studied
Various cKeller
(2022) [62]		2571 children (37)Juvenile autoimmune rheumatic diseases on immune-suppressive treatment9 studies showed seroconversion rates lower in children with juvenile autoimmune rheumatic diseases on immune-suppressive treatment compared with control children, but many other studies were underpowered to demonstrate differencesNot studied
Various d,eTse (2020) [63]2468 children (37)Children with autoimmune diseases on immune modulatory drug therapyPatients on biologics mounted adequate seroprotective responses, but antibody titers tended to be lower. Patients on steroids had decreased seroconversion (60% for influenza vaccine). Patients on cyclophosphamide had decreased seroconversion (50% for HPV vaccine) Not studied
a Included 9-valent pneumococcal conjugate vaccine, BCG, Hib; b included diphtheria, HAV, HBV, HPV, influenza, pertussis, pneumococcus, and VZV vaccines; c included diphtheria, HAV, HBV, HPV, influenza, measles, mumps, meningococcal C, pneumococcus, rubella, tetanus, and VZV vaccines; d included HAV, HBV, HPV, influenza, measles, mumps, rubella, tetanus, and VZV vaccines; e included patients with autologous stem-cell transplant, hematological cancer, HIV infection, renal transplant, and solid tumor under chemotherapy. BCG: Bacillus Calmette–Guérin; HAV: hepatitis A virus; HBV: hepatitis B virus; Hib: Haemophilus influenzae type b; HIV: human immunodeficiency virus; HPV: human papillomavirus; IC: immunocompromised; PCV: pneumococcal conjugate vaccine; PPSV: pneumococcal polysaccharide vaccine; Ref: reference; SLE: systemic lupus erythematosus; TNF: tumor necrosis factor; VZV: varicella-zoster virus; ZVL, live-attenuated zoster vaccine; VZVsub, recombinant subunit zoster vaccine.
Table
Table 4. Vaccine seroconversion response categories.
Table 4. Vaccine seroconversion response categories.
CategoryGeneral Seroconversion RatesIC TypesSuggested Management
Good responseAbout >60% compared to healthy controls
  • Chronic kidney disease requiring hemodialysis or peritoneal dialysis
  • HIV (normal CD4 counts)
  • Immune-mediated inflammatory diseases (e.g., RA, SLE)
  • Inflammatory bowel disease
  • Multiple sclerosis (treated)
  • Post-splenectomy status
  • Solid tumors
  • Follow usual vaccination regime (including any booster doses), by default
  • Time vaccination when least immunosuppressed
Intermediate responseAbout 40–60% compared to healthy controls
  • Anti-CTLA-4 therapy
  • Hematologic cancer
  • HIV (low CD4 counts)
  • Time vaccination when least immunosuppressed
  • Shielding measures a
  • Consider high-dose vaccine, revaccination when less immunosuppressed
Poor responseAbout <40% compared to healthy controls
  • B-cell-depleting agents (e.g., anti-CD20 therapy)
  • Hematopoietic stem-cell transplant recipients
  • Liver cirrhosis
  • Solid organ transplant recipient
  • Time vaccination when least immunosuppressed
  • Shielding measures a
  • Consider high-dose vaccine, revaccination when less immunosuppressed
  • Consider checking seroconversion. If nonresponse, consider booster doses or long-acting monoclonal antibodies for pre-exposure prophylaxis b
a Examples include face mask use, hand hygiene, and physical distancing for respiratory pathogens; b examples include tixagevimab–cilgavimab for COVID-19. CTLA-4: cytotoxic T-lymphocyte antigen-4; HIV: human immunodeficiency virus; IC: immunocompromised; RA: rheumatoid arthritis; SLE: systemic lupus erythematosus.
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Share and Cite

MDPI and ACS Style

See, K.C. Vaccination for the Prevention of Infection among Immunocompromised Patients: A Concise Review of Recent Systematic Reviews. Vaccines 2022, 10, 800. https://doi.org/10.3390/vaccines10050800

AMA Style

See KC. Vaccination for the Prevention of Infection among Immunocompromised Patients: A Concise Review of Recent Systematic Reviews. Vaccines. 2022; 10(5):800. https://doi.org/10.3390/vaccines10050800

Chicago/Turabian Style

See, Kay Choong. 2022. "Vaccination for the Prevention of Infection among Immunocompromised Patients: A Concise Review of Recent Systematic Reviews" Vaccines 10, no. 5: 800. https://doi.org/10.3390/vaccines10050800

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Metrics

Back to TopTop